This is an application for continued funding for an existing adult AIDS Clinical Trials Unit (ACTU) at The University of Texas Medical Branch at Galveston. The primary objective is to support the scientific agenda of the AIDS Clinical Trial Group (ACTG) in conducting clinical trials whose goals are to improve the therapy of HIV disease and it complications and to aid in understanding the pathogenesis of HIV-associated disease. The specific aims include: (1) to enroll at least 110 patients per year into ACTG-sponsored trials and to emphasize women and minority participation in these trials; (2) to perform all laboratory-based services that are required for completion of clinical trials and to continue to contribute to the development of novel laboratory-based assays that permit the ACTG to develop innovative therapeutic protocols; (3) to contribute especially to the ACTG's Immunology and Immune-based Therapy agenda and (4) to be centrally involved, through the ACTG structure, in the development of pathogenesis testing, hypothesis- driven clinical trials. These aims will be achieved by continuing to employ the considerable skills of the clinical and laboratory- based personnel who have contributed to the past performance of this ACTU. Participation in HIV Disease protocols will emphasize those that employ currently approved agents and agents under active investigation in combinations that inhibit viral replication at different points in the replicative cycle in an effort to maximally reduce viral burden. These studies can more clearly define the role that viral burden plays in disease progression and can validate this marker as a useful endpoint in clinical trials and as a useful guide to therapy in clinical practice. As new agents become available, early phase trials will be done to demonstrate safety and efficacy so that these agents can be used in the manner described above. Complications of HIV Disease protocols conducted at this ACTU will focus on the reasons for failure of current prophylactic regimens as well as the identification of specific risk factors for opportunistic infections so that prophylactic strategies can be targeted to those who are at highest risk. These efforts should result in less complicated therapeutic regimens for people being treated for HIV. Continued participation in Neurology trials and, to a more limited extent, Oncology trials, is also planned. Finally, the exploration of immune-based therapies is a priority that will be facilitated by continued involvement in committees that shape the immunology agenda and laboratory expertise in supporting immunology-based studies.